An opinionated take on NEJM highlights for February 2018


A-fib in heart failure – time to be aggressive

Over the last 15 years, there has been a growing body of evidence for the effectiveness of catheter ablation to treat atrial fibrillation (a-fib), a condition for which the standard of care has been anti-arrhythmic medications. A-fib commonly coexists with heart failure but until now it has not been clear whether medication or catheter ablation would be the preferred treatment – we now have the answer, at least for patients with a substantially reduced ejection fraction. In a randomized trial of ~350 patients, the medication arm’s death rate was about 25% at 3 years – double what was seen in the ablated group. Given the large population, expect cardiac electrophysiologists and their interventional suites to be very busy. Catheter Ablation for Atrial Fibrillation with Heart Failure; Paradigm Shift for Treatment of Atrial Fibrillation in Heart Failure (subscriber access)


The future is here: cancer-agnostic mutation-directed therapy

Following the 2017 FDA approval of pembrolizumab (Keytruda, Merck) for all and any cancers exhibiting specified genetic defects, mindsets are shifting away from an organ-centered view of cancer – and it’s clearly justified in the case of larotrectinib (Loxo Oncology), a kinase inhibitor directed at TRKs (tropomyosin receptor kinases) which are found to be abnormally activated in a small fraction of cancers (~1%). A report describing larotrectinib’s activity in 55 patients of all ages (infant to elderly), in a broad range of solid non-CNS solid tumors (12 types), shows a response rate of 80% with most of these responses durable. And to put the cherry on the cake, the genetic features for drug resistance of the non-responders/relapsers were analyzed and a follow-on compound from Loxo has been designed to overcome this resistance.  Of note though, post-hoc analysis of the non-responders showed that some of them were false positive for TRK activation which underlines the importance of validated, robust companion diagnostics for this kind of development strategy. Still, this is more and more the future of oncology.  Efficacy of Larotrectinib in TRK Fusion–Positive Cancers in Adults and Children; Developing Anticancer Drugs in Orphan Molecular Entities — A Paradigm under Construction (subscriber access)


The New England Journal of Medicine is a premier weekly medical journal covering many topics of interest to the health sector. In this monthly series we offer an opinionated perspective on selected highlights that might be of interest to our clients and others.